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The purpose of this study is to evaluate the efficacy and safety of repeated doses of ecallantide in the treatment of acute attacks of hereditary angioedema and to allow HAE patients continued access to ecallantide. In addition, patients enrolled in DX-88/20 (EDEMA4) trial will be followed up and treated for subsequent attacks in this trial.
This is an open label trial.
The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide in the treatment of acute attacks of hereditary angioedema. This study is designed to provide efficacy and safety data on repeated use of ecallantide. These data are intended to support the marketing authorization of ecallantide in the treatment of acute attacks of hereditary angioedema. Efficacy and safety of ecallantide will be evaluated in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DX-88 (ecallantide) | Experimental | DX-88 (ecallantide) Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ecallantide | Drug | solution for SC injection, one 30 mg dose per HAE attack |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | Mean Symptom Complex Severity (MSCS) score is a validated point-in-time measure of symptom severity. At baseline and 4 hrs, patients rated the severity on a categorical scale (0=normal, 1=mild, 2=moderate, 3=severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more. | 4 hrs post dose after every episode |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | The Treatment Outcome Score (TOS)is a validated measure of response to therapy. Response assessment for each symptom complex (internal head/neck, stomach/GI, genital/buttocks, external head/neck or cutaneous) was to be weighted based on the severity of symptom complexes at baseline. Severity assessment at baseline was rated on a categorical scale (1=mild, 2=moderate, 3=severe) for symptoms at each affected symptom complex. Response assessment of each symptom complex post-dosing relative to baseline used a scale (100=significant improvement, 50=improvement, 0=same). The weighted values were used to calculate the composite TOS. A TOS greater than 0 denotes an improvement in symptoms compared with baseline severity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aaron Davis | Scottsdale | Arizona | 85251 | United States | ||
| Arkansas Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24712435 | Derived | Rubinstein E, Stolz LE, Sheffer AL, Stevens C, Bousvaros A. Abdominal attacks and treatment in hereditary angioedema with C1-inhibitor deficiency. BMC Gastroenterol. 2014 Apr 9;14:71. doi: 10.1186/1471-230X-14-71. | |
| 23878046 | Derived | MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013 Aug;132(2):e490-7. doi: 10.1542/peds.2013-0646. Epub 2013 Jul 22. |
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| ID | Title | Description |
|---|---|---|
| FG000 | DX-88 (Ecallantide) | Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| 4 hrs post dose after every episode |
| Time to Significant Improvement | Time to significant improvement in overall response based on the period from 15 minutes after dosing through 4 hrs post dosing. Significant improvement was defined as a response of "a lot better or resolved" in the overall response assessment. | 15 min - 4 hrs post dose after every episode |
| Little Rock |
| Arkansas |
| 72202 |
| United States |
| Little Rock Allergy & Asthma Clinic | Little Rock | Arkansas | 72205 | United States |
| Alta Bates Summit Comprehensive Cancer Center | Berkeley | California | 94704 | United States |
| Pacific Coast Allergy | Crescent City | California | 95531 | United States |
| Jacob Offenberger | Granada Hills | California | 91344 | United States |
| UCLA David Geffen School of Medicine, Department of Medicine | Los Angeles | California | 90095-1680 | United States |
| Asthma and Allergy Associates, P.C. | Colorado Springs | Colorado | 80907 | United States |
| Christiana Hospital, Christiana Care Health Services | Newark | Delaware | 19718 | United States |
| Georgetown University Medical Center, Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| University of Miami, General Clinical Research Center | Miami | Florida | 33136 | United States |
| University of South Florida, Asthma, Allergy and Immunology Clinical Research Unit | Tampa | Florida | 33613 | United States |
| Roberson Allergy and Asthma | West Palm Beach | Florida | 33401 | United States |
| Family Allergy & Asthma Center, PC | Atlanta | Georgia | 30342 | United States |
| Allergy Center of Brookstone | Columbus | Georgia | 31904 | United States |
| University Consultants in Allergy and Immunology | Chicago | Illinois | 60612 | United States |
| Muncie Allergy Center | Muncie | Indiana | 47304 | United States |
| Kansas City Allergy & Asthma | Overland Park | Kansas | 66210 | United States |
| Institute for Asthma and Allergy | Wheaton | Maryland | 20902 | United States |
| Brigham and Women's Hospital | Chestnut Hill | Massachusetts | 02467 | United States |
| Asthma and Allergy Institutes of Michigan | Clinton Township | Michigan | 48038 | United States |
| Respiratory Medicine Research Institute of Michigan, PLC | Ypsilanti | Michigan | 48197 | United States |
| Nevada Access to Research and Education Society | Las Vegas | Nevada | 89102 | United States |
| University of Nevada School of Medicine | Reno | Nevada | 89503 | United States |
| UMDNJ- New Jersey Medical School | Newark | New Jersey | 07103 | United States |
| Allergy Partners of Albuquerque | Albuquerque | New Mexico | 87109 | United States |
| Winthrop University Hospital | Mineola | New York | 11501 | United States |
| Allergy Partners of Western North Carolina | Asheville | North Carolina | 28801 | United States |
| University of Cincinnati, Division of Internal Medicine | Cincinnati | Ohio | 45267 | United States |
| Optimed Research, LLC | Columbus | Ohio | 43235 | United States |
| Penn State Milton S Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| Asthma Allergy and Pulmonary Associates | Philadelphia | Pennsylvania | 19107 | United States |
| Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Highlands Allergy and Asthma Center, PC | Bristol | Tennessee | 37620 | United States |
| The Paull Allergy and Asthma Clinic, P.A | Bryan | Texas | 77802 | United States |
| AARA Research Center | Dallas | Texas | 75231 | United States |
| University of Utah Health Sciences Center | Salt Lake City | Utah | 84132-2409 | United States |
| Clinical Research Associates of Tidewater | Norfolk | Virginia | 23507 | United States |
| Puget Sound Allergy, Asthma, & Immunology | Tacoma | Washington | 98405 | United States |
| Allergy and Asthma Research Centre | Ottawa | Ontario | K1Y 4G2 | Canada |
| Jordan University Hospital | Amman | 1194 | Jordan |
| 23548529 | Derived | Sheffer AL, MacGinnitie AJ, Campion M, Stolz LE, Pullman WE. Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Mar;110(3):184-188.e2. doi: 10.1016/j.anai.2012.12.007. Epub 2013 Jan 5. |
| 23548526 | Derived | Li HH, Campion M, Craig TJ, Soteres DF, Riedl M, Lumry WR, MacGinnitie AJ, Shea EP, Bernstein JA. Analysis of hereditary angioedema attacks requiring a second dose of ecallantide. Ann Allergy Asthma Immunol. 2013 Mar;110(3):168-72. doi: 10.1016/j.anai.2012.12.004. Epub 2013 Jan 8. |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | DX-88 (ecallantide) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | Mean Symptom Complex Severity (MSCS) score is a validated point-in-time measure of symptom severity. At baseline and 4 hrs, patients rated the severity on a categorical scale (0=normal, 1=mild, 2=moderate, 3=severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more. | All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in MSCS score. | Posted | Mean | Standard Deviation | scores on a scale | 4 hrs post dose after every episode |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | The Treatment Outcome Score (TOS)is a validated measure of response to therapy. Response assessment for each symptom complex (internal head/neck, stomach/GI, genital/buttocks, external head/neck or cutaneous) was to be weighted based on the severity of symptom complexes at baseline. Severity assessment at baseline was rated on a categorical scale (1=mild, 2=moderate, 3=severe) for symptoms at each affected symptom complex. Response assessment of each symptom complex post-dosing relative to baseline used a scale (100=significant improvement, 50=improvement, 0=same). The weighted values were used to calculate the composite TOS. A TOS greater than 0 denotes an improvement in symptoms compared with baseline severity. | All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in TOS score. | Posted | Mean | Standard Deviation | scores on a scale | 4 hrs post dose after every episode |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Time to Significant Improvement | Time to significant improvement in overall response based on the period from 15 minutes after dosing through 4 hrs post dosing. Significant improvement was defined as a response of "a lot better or resolved" in the overall response assessment. | All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in TOS score. | Posted | Median | 95% Confidence Interval | estimated time in minutes | 15 min - 4 hrs post dose after every episode |
|
|
pre-dose to 28 days (+/-2 days) post dose
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | DX-88 (ecallantide) | 27 | 147 | 102 | 147 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hereditary angioedema | Congenital, familial and genetic disorders | MedDRA (10.0) | Systematic Assessment |
| |
| hypersensitivity | Immune system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| anaphylactic reaction | Immune system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| anemia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| abdominal distension | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| cholecystitis | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
| |
| otitis externa | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| cellulitis staphyloccal | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
| |
| contusion | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
| |
| transfusion reaction | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
| |
| liver function test abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| white blood cell count increased | Investigations | MedDRA (10.0) | Systematic Assessment |
| |
| dehydration | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
| |
| chronic myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
| |
| lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
| |
| anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
| |
| laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| erythema | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
| |
| homicide | Social circumstances | MedDRA (10.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hereditary angioedema | Congenital, familial and genetic disorders | MedDRA (10.0) | Systematic Assessment |
| |
| nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
| |
| abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| diarrhoea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| |
| anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
Dyax agreements vary, but Dyax will not prohibit any investigator from publishing. Dyax reviews publications prior to public release and can request deferral by up to 60 days beyond the proposed publication date if necessary to preserve its intellectual property. Dyax can request changes to publications to remove non-study-related confidential information. Dyax can also request deferral of single-center publications until after disclosure of the clinical trial's primary publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |
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| ID | Term |
|---|---|
| C511194 | ecallantide |
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| Jordan |
|
|
| change in MSCS at 4 hrs episode 4 (n=52) |
|
| change in MSCS at 4 hrs episode 5 (n=38) |
|
| change in MSCS at 4 hrs episode 6 (n=32) |
|
| change in MSCS at 4 hrs episode 7 (n=25) |
|
| change in MSCS at 4 hrs episode 8 (n=22) |
|
| change in MSCS at 4 hrs episode 9 (n=22) |
|
| change in MSCS at 4 hrs episode 10 (n=16) |
|
| change in MSCS at 4 hrs episode 11 (n=16) |
|
| change in MSCS at 4 hrs episode 12 (n=12) |
|
| change in MSCS at 4 hrs episode 13 (n=12) |
|
| Units | Counts |
|---|
| Participants |
|
|
|